Chemotherapy and its Adverse Effects – A Systematic Review

 

Simrat Kaur, Prempati Mayanglambam, Deepika Bajwan, Nancy Thakur

School of Nursing, Galgotias University, U.P, JINS, Kolkata, West Bengal.

*Corresponding Author E-mail: simrat.kaur@galgotiasuniversity.edu.in

 

 

ABSTRACT:

Chemotherapy is an aggressive form of chemical drug therapy meant to destroy rapidly growing cells in the body. It’s usually used to treat cancer, as cancer cells grow and divide faster than other cells. Chemotherapy is often used in combination with other therapies, such as surgery, radiation, or hormone therapy. Usually, cancer drugs work by damaging the RNA or DNA that tells the cell how to copy itself in division. If the cancer cells are unable to divide, they die. The faster that cancer cells divide, the more likely it is that chemotherapy will kill the cells, causing the tumor to shrink. They also induce cell suicide (self-death or apoptosis). Chemotherapy drugs that kill cancer cells only when they are dividing are called cell-cycle specific. Chemotherapy drugs that kill cancer cells when they are at rest are called cell-cycle non-specific. The scheduling of chemotherapy is set based on the type of cells, rate at which they divide, and the time at which a given drug is likely to be effective. This is why chemotherapy is typically given in cycles. Chemotherapy is most effective at killing cells that are rapidly dividing.

 

KEYWORDS: Cancer, chemotherapy, hormone.

 

 


INTRODUCTION:

Cancerous tumors are characterized by cell division, which is no longer controlled as it is in normal tissue. "Normal" cells stop dividing when they come into contact with like cells, a mechanism known as contact inhibition. Cancerous cells lose this ability. Pictures of cancer cells show that cancerous cells lose the ability to stop dividing when they contact similar cells. Cancer cells no longer have the normal checks and balances in place that control and limit cell division. The process of cell division, whether normal or cancerous cells, is through the cell cycle. The cell cycle goes from the resting phase, through active growing phases, and then to mitosis (division).The ability of chemotherapy to kill cancer cells depends on its ability to halt cell division.

 

The use of combination therapy depends on:

·       The stage and type of cancer

·       Overall health

·       Previous cancer treatments

·       The location of the cancer cells

 

It’s considered a systemic treatment, which means it affects the entire body.

 

Chemotherapy has been proven to effectively attack cancer cells, but it can cause serious side effects that can severely impact your quality of life.

 

Why chemotherapy is used:

Chemotherapy is primarily used to:

·       Lower the total number of cancer cells in your body

·       Reduce the likelihood of cancer spreading

·       Shrink tumor size

·       Reduce current symptoms

 

Types of chemotherapy:

There are many chemotherapy drugs that are grouped into classes depending on how they work. Combining chemotherapy drugs from different classes can make the treatment work better because the different drugs attack cancer cells at different points in their growth cycle. It may also prevent resistance and help lower the chance of cancer coming back (recurrence).

 

Some types of chemotherapy include:

·       DNA-damaging agents are also called alkylating agents. They stop cells from dividing by changing the cell’s DNA so it can’t be copied. Because cancer cells grow and divide quickly, they end up dying because they don’t have time to repair the damaged DNA.

·       Antimetabolites act like the building blocks of DNA or RNA

·       That cancer cells need to grow and survive. When a cancer cell uses the antimetabolite chemotherapy drug instead of their own substances, the DNA is damaged and the cell dies.

·       Antimitotics block the process of cell division called mitosis so cells can’t divide and multiply.

·       Antitumour antibiotics bind to DNA so it can’t work properly. This causes the cell to die. These drugs are different than antibiotics used to treat infection.

·       DNA-repair enzyme inhibitors prevent the normal repair of DNA damage inside the cell. These chemotherapy drugs attack the

·       Enzymes that normally repair damage to DNA. If a cancer cell can’t repair damage to DNA, it dies.

 

Adverse effects:

Chemotherapeutic techniques have a range of side effects that depend on the type of medications used. The most common medications affect mainly the fast-dividing cells of the body, such as blood cells and the cells lining the mouth, stomach, and intestines. Chemotherapy-related toxicities can occur acutely after administration, within hours or days, or chronically, from weeks to years.

 

Immunosuppression and myelosuppression:

Virtually all chemotherapeutic regimens can cause depression of the immune system, often by paralysing the bone marrow and leading to a decrease of white blood cells, red blood cells, and platelets. Anemia and thrombocytopenia may require blood transfusion. Neutropenia (a decrease of the neutrophil granulocyte count below 0.5 x 109/litre) can be improved with synthetic G-CSF (granulocyte-colony-stimulating factor, e.g., filgrastim, lenograstim).

 

In very severe myelosuppression, which occurs in some regimens, almost all the bone marrow stem cells (cells that produce white and red blood cells) are destroyed, meaning allogenic or autologous bone marrow cell transplants are necessary. (In autologous BMTs, cells are removed from the person before the treatment, multiplied and then re-injected afterward; in allogenic BMTs, the source is a donor.) However, some people still develop diseases because of this interference with bone marrow.

 

Neutropenic enterocolitis:

Due to immune system suppression, neutropenic enterocolitis (typhlitis) is a "life-threatening gastrointestinal complication of chemotherapy. Typhlitis is an intestinal infection which may manifest itself through symptoms including nausea, vomiting, diarrhea, a distended abdomen, fever, chills, or abdominal pain and tenderness.

 

Typhlitis is a medical emergency. It has a very poor prognosis and is often fatal unless promptly recognized and aggressively treated Successful treatment hinges on early diagnosis provided by a high index of suspicion and the use of CT scanning, nonoperative treatment for uncomplicated cases, and sometimes elective right hemicolectomy to prevent recurrence.

 

Gastrointestinal distress:

Nausea, vomiting, anorexia, diarrhoea, abdominal cramps, and constipation are common side-effects of chemotherapeutic medications that kill fast-dividing cells. Malnutrition and dehydration can result when the recipient does not eat or drink enough, or when the person vomits frequently, because of gastrointestinal damage. This can result in rapid weight loss, or occasionally in weight gain, if the person eats too much in an effort to allay nausea or heartburn. Weight gain can also be caused by some steroid medications. These side-effects can frequently be reduced or eliminated with antiemetic drugs. Low-certainty evidence also suggests that probiotics may have a preventative and treatment effect of diarrhoea related to chemotherapy alone and with radiotherapy. However, a high index of suspicion is appropriate, since diarrhoea and bloating are also symptoms of typhlitis, a very serious and potentially life-threatening medical emergency that requires immediate treatment.

 

Anaemia:

Anemia can be a combined outcome caused by myelosuppressive chemotherapy, and possible cancer-related causes such as bleeding, blood cell destruction (hemolysis), hereditary disease, kidney dysfunction, nutritional deficiencies or anemia of chronic disease. Treatments to mitigate anemia include hormones to boost blood production (erythropoietin), iron supplements, and blood transfusions. Myelosuppressive therapy can cause a tendency to bleed easily, leading to anemia. Medications that kill rapidly dividing cells or blood cells can reduce the number of platelets in the blood, which can result in bruises and bleeding. Extremely low platelet counts may be temporarily boosted through platelet transfusions and new drugs to increase platelet counts during chemotherapy are being developed. Sometimes, chemotherapy treatments are postponed to allow platelet counts to recover.

 

Fatigue may be a consequence of the cancer or its treatment, and can last for months to years after treatment. One physiological cause of fatigue is anemia, which can be caused by chemotherapy, surgery, radiotherapy, primary and metastatic disease or nutritional depletion. Aerobic exercise has been found to be beneficial in reducing fatigue in people with solid tumours.

 

Nausea and vomiting:

Nausea and vomiting are two of the most feared cancer treatment-related side-effects for people with cancer and their families. Up to 20% of people receiving highly emetogenic agents in this era postponed, or even refused potentially curative treatments. Chemotherapy-induced nausea and vomiting (CINV) are common with many treatments and some forms of cancer.. Effective mediation of these unpleasant and sometimes-crippling symptoms results in increased quality of life for the recipient and more efficient treatment cycles, due to less stoppage of treatment due to better tolerance and better overall health.

 

Hair loss:

Hair loss (alopecia) can be caused by chemotherapy that kills rapidly dividing cells; other medications may cause hair to thin. These are most often temporary effects: hair usually starts to regrow a few weeks after the last treatment, but sometimes with a change in color, texture, thickness or style. Sometimes hair has a tendency to curl after regrowth, resulting in "chemo curls." Severe hair loss occurs most often with drugs such as doxorubicin, daunorubicin, paclitaxel, docetaxel, cyclophosphamide, ifosfamide and etoposide. Permanent thinning or hair loss can result from some standard chemotherapy regimens.

 

Chemotherapy induced hair loss occurs by a non-androgenic mechanism, and can manifest as alopecia totalis, telogen effluvium, or less often alopecia areata. It is usually associated with systemic treatment due to the high mitotic rate of hair follicles, and more reversible than androgenic hair loss, although permanent cases can occur. Chemotherapy induces hair loss in women more often than men.

 

Scalp cooling offers a means of preventing both permanent and temporary hair loss; however, concerns about this method have been raised.

 

Infertility:

Some types of chemotherapy are gonadotoxic and may cause infertility. Chemotherapies with high risk include procarbazine and other alkylating drugs such as cyclophosphamide, ifosfamide, busulfan, melphalan, chlorambucil, and chlormethine. Drugs with medium risk include doxorubicin and platinum analogs such as cisplatin and carboplatin.  On the other hand, therapies with low risk of gonadotoxicity include plant derivatives such as vincristine and vinblastine, antibiotics such as bleomycin and dactinomycin, and antimetabolites such as methotrexate, mercaptopurine, and 5-fluorouracil.

Female infertility by chemotherapy appears to be secondary to premature ovarian failure by loss of primordial follicles. This loss is not necessarily a direct effect of the chemotherapeutic agents, but could be due to an increased rate of growth initiation to replace damaged developing follicles.

People may choose between several methods of fertility preservation prior to chemotherapy, including cryopreservation of semen, ovarian tissue, oocytes, or embryos.  As more than half of cancer patients are elderly, this adverse effect is only relevant for a minority of patients.

 

In chemotherapy as a conditioning regimen in hematopoietic stem cell transplantation, a study of people conditioned with cyclophosphamide alone for severe aplastic anemia came to the result that ovarian recovery occurred in all women younger than 26 years at time of transplantation, but only in five of 16 women older than 26 years.

 

Peripheral neuropathy:

Between 30 and 40 percent of people undergoing chemotherapy experience chemotherapy-induced peripheral neuropathy (CIPN), a progressive, enduring, and often irreversible condition, causing pain, tingling, numbness and sensitivity to cold, beginning in the hands and feet and sometimes progressing to the arms and legs. Chemotherapy drugs associated with CIPN include thalidomide, epothilones, vinca alkaloids, taxanes, proteasome inhibitors, and the platinum-based drugs. Whether CIPN arises, and to what degree, is determined by the choice of drug, duration of use, the total amount consumed and whether the person already has peripheral neuropathy. Though the symptoms are mainly sensory, in some cases motor nerves and the autonomic nervous system are affected. CIPN often follows the first chemotherapy dose and increases in severity as treatment continues, but this progression usually levels off at completion of treatment. The platinum-based drugs are the exception; with these drugs, sensation may continue to deteriorate for several months after the end of treatment. Some CIPN appears to be irreversible. Pain can often be managed with drug or other treatment but the numbness is usually resistant to treatment.

 

Cognitive impairment:

Some people receiving chemotherapy report fatigue or non-specific neurocognitive problems, such as an inability to concentrate; this is sometimes called post-chemotherapy cognitive impairment, referred to as "chemo brain" in popular and social media.

 

Organ damage:

Cardiotoxicity (heart damage) is especially prominent with the use of anthracycline drugs (doxorubicin, epirubicin, idarubicin, and liposomal doxorubicin). The cause of this is most likely due to the production of free radicals in the cell and subsequent DNA damage. Other chemotherapeutic agents that cause cardiotoxicity, but at a lower incidence, are cyclophosphamide, docetaxel and clofarabine.

 

Hepatotoxicity (liver damage) can be caused by many cytotoxic drugs. The susceptibility of an individual to liver damage can be altered by other factors such as the cancer itself, viral hepatitis, immunosuppression and nutritional deficiency. The liver damage can consist of damage to liver cells, hepatic sinusoidal syndrome (obstruction of the veins in the liver), cholestasis (where bile does not flow from the liver to the intestine) and liver fibrosis.

 

Nephrotoxicity (kidney damage) can be caused by tumor lysis syndrome and also due direct effects of drug clearance by the kidneys. Different drugs will affect different parts of the kidney and the toxicity may be asymptomatic (only seen on blood or urine tests) or may cause acute kidney injury.

 

Ototoxicity (damage to the inner ear) is a common side effect of platinum based drugs that can produce symptoms such as dizziness and vertigo. Children treated with platinum analogues have been found to be at risk for developing hearing loss.

 

CONCLUSION:

Chemotherapy is a type of cancer treatment. Also called “chemo,” it’s one of several cancer treatments that use drugs against various types of cancer. Other drug therapies include: Hormone therapy, or drugs that prevent certain cancers from getting the hormones they need to grow. Immunotherapy, or drugs that help your immune system fight cancer. Targeted therapy, or drugs that change how cancer cells multiply and behave. Chemotherapy (anti-neoplastic drugs) is divided into five classes based on how they work to kill cancer. Although these drugs are divided into groups, there is some overlap among some of the specific drugs. Further sections discuss several different types of chemotherapy in the effort to further explain these important procedures.

 

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Received on 25.08.2022           Modified on 17.09.2022

Accepted on 14.10.2022          © A&V Publications all right reserved

Int. J. Nur. Edu. and Research. 2022; 10(4):399-402.

DOI: 10.52711/2454-2660.2022.00090